Ramachary-Bressy-Wang [3+2]cycloaddition reaction: Synthesis of fully decorated 1,2,3-triazoles as potent anticancer and EGFR inhibitors

• Published in: Journal of molecular structure Vol. 1262; p. 132975
• Main Authors: N, Manoj Kumar, Nukala, Satheesh Kumar, Thirukovela, Narasimha Swamy, Sreerama, Rakesh, E, Ramya Sucharitha, Kamarajugadda, Pavan, Narsimha, Sirassu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-08-2022
• Subjects: 1,2,3-triazoles; ADME; Anticancer activity; Benzimidazole; Coumarine; EGFR; Coumarine; ADME; Benzimidazole; 1,2,3-triazoles; EGFR; Anticancer activity
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132975

•Organocatalytic synthesis of novel fully decorated 1,2,3-triazoles (5a-5m & 6a-6e).•The compounds 5f, 5j, 5k, 5l and 5m exhibited promising in vitro anticancer activity against MCF-7, A-549, and HeLa cell lines.•The compounds 5k and 5m showed nearly double the potency against epidermal growth factor receptor (EGFR) than the reference drug erlotinib.•Results of in silico molecular docking and ADME studies of 5f, 5j, 5k, 5l and 5m were also supported the observed in vitro anticancer and EGFR kinase inhibitory activity data.
A general strategy was developed for the synthesis of new fully decorated 1,2,3-triazoles (5a-m & 6a-e) containing coumarine and sulfonyl-benzimidazole from 3-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)sulfonyl)acetyl)-2H-chromen-2-one and several azides using Ramachary-Bressy-Wang organocatalytic cycloaddition method. In vitro anticancer activity of all these derivatives revealed that five compounds like 5f, 5j, 5k, 5l and 5m were active against three human cancer cell lines like breast carcinoma (MCF-7), cervical carcinoma (HeLa) and alveolar carcinoma (A-549). In specific, compounds 5k and 5m showed superior activity against MCF-7 and HeLa cell lines than the standard drugs Doxorubicin and Erlotinib. Later, the results of inhibitory assay of potent compounds 5f, 5j, 5k, 5l and 5m against the tyrosine kinase EGFR revealed that compounds 5k and 5m showed nearly double the potency of the reference drug erlotinib. The in silico studies of five potent compounds 5f, 5j, 5k, 5l and 5m were also carried out to identify the interactions against EGFR receptor and found that the energy calculations were covenant with the obtained IC50 values. Finally, in silico pharmacokinetic profile was predicted for five potent compounds using SWISS/ADME and pkCSM, where all the five compounds followed Lipinski and Veber rule without any deviation.
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